Human Sensory LTP Predicts Memory Performance and Is Modulated by the BDNF Val66Met Polymorphism

Abstract

Background : Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val 66 Met; a single-nucleotide polymorphism (SNP) implicated in memory function. Methods : Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP- like enhancements of the visually-evoked response, and a test of visual memory. Results : The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance. Conclusions : The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.

Investigating the Influence of the Brain-Derived Neurotrophic Factor Val66Met Single Nucleotide Polymorphism on Familiarity and Recollection Event-Related Potentials

“…Behaviourally, we replicated previous work reporting that Met allele carriers have 31 VAL66MET GENOTYPE INFLUENCES RECOGNITION ERPs reduced accuracy compared to Val/Val individuals on recognition memory tasks Hariri et al, 2003;Spriggs et al, 2019) . More specifically, we found anecdotal evidence in support of Val/Val individuals outperforming Met allele carriers on the item-recognition portion of our task.…”

“…For example, a single nucleotide polymorphism (SNP) known as the Val66Met SNP (rs6265), occurs within the gene coding for brain-derived neurotrophic factor (BDNF) and has been previously related to reduced accuracy on a large number of memory tasks (Dempster et al, 2005;Egan et al, 2003;Hariri et al, 2003;Kennedy et al, 2015;Lamb, Thompson, McKay, Waldie, & Kirk, 2015) . Several recent studies have reported that carriers of this SNP perform worse than non-carriers on recognition memory tasks (Komulainen et al, 2008;Spriggs et al, 2019) . The Val66Met SNP is a non-synonymous SNP that results in a switch from a valine (Val) to methionine (Met) amino acid.…”

“…This new amino acid impacts the trafficking of the resulting BDNF protein and its activity-dependent secretion (Chen et al, 2004) . These biological changes are thought to influence memory formation by impacting context-specific synaptic plasticity (Schofield et al, 2009;Spriggs et al, 2019) , an important mechanism underpinning learning and memory.…”

The Effects of Human Visual Sensory Stimuli on N1b Amplitude: An EEG Study

“…Moreover, the processing of sensory information in simple tasks (e.g., visual sensory stimuli) is further modulated by attention [ 4 ]. Altered processing of sensory information can impact the activity of other systems (e.g., memory systems) [ 5 ], therefore, the N1b component may be a marker indicating the effects of attention on memory. The N1b component is a late phase of the N1 complex that is a negative ERP signal occurring ~170–190-ms post stimulus onset [ 6 , 7 ].…”

The Brain-Derived Neurotrophic Factor Val66Met Genotype Does Not Influence the Grey or White Matter Structures Underlying Recognition Memory

“…Previous studies have found that individuals with at least one copy of the Val66Met minor allele (i.e., Val/Met and Met/Met) fare worse on learning and memory tasks (Bekinschtein, Cammarota, Izquierdo, & Medina, 2008;Lamb, Thompson, McKay, Waldie, & Kirk, 2015;Pang & Lu, 2004;Rattiner, Davis, & Ressler, 2005;Spriggs et al, 2019;Tyler, Alonso, Bramham, & Pozzo-Miller, 2002). For example, Egan et al (2003) reported that Met allele carriers performed significantly worse on episodic memory, as measured by the revised version of the Wechsler Memory Scale (WMS-R).…”